Predicting the risk of uterine fibroids in female copper smelter workers by cytogenetic abnormalities of buccal epithelium

Abstract

Exposure to adverse occupational factors increases the risk of diseases of the reproductive system. Long-term studies have shown a high prevalence of uterine fibroids among all diseases of the reproductive system in women exposed to occupational hazards in industry. The occurrence of fibroids, having such complications as menorrhagia, pain in the pelvic area, and infertility, hampers performance and diminishes the quality of life. The risk of genetic mutations in cells playing a key role in the development of fibroids is raised by inhalation of industrial aerosols containing metals possessing mutagenic and carcinogenic potencies. Cytology of the buccal epithelium can be used as a method objectively indicating the genetic risk. The purpose of the study was to develop a predictive model for assessing the risk of uterine fibroids in female workers exposed to aerosols containing metal particles at a copper smelter using buccal cytograms. We examined 47 female workers of a copper smelter, of which 39 formed the main (exposed) group. Uterine fibroids were more frequent in the main group than in the controls (25.6 % versus 0.0 %, p ≤ 0.05). Genotoxic indicators, such as protrusions and micronuclei, and cytotoxicity indicators were also significantly increased in this group (nuclear vacuolization and cytoplasmic vacuolation were 1.6 times and karyolysis 1.8 times higher compared with the controls, p ≤ 0.05). We have developed two mathematical models for assessing the risk of uterine fibroids. Model 1 includes variables without restrictions of characteristics, i.e. micronuclei, perinuclear vacuoles, and cytoplasmic vacuolation (AUROC – 0.940), while Model 2 necessarily includes such genotoxic parameters as micronuclei and protrusions (AUROC – 0.883). The 4-member model (M1+M2), which includes both genotoxic (micronuclei and protrusions) and cytotoxic (binucleated cells and cytoplasmic vacuolation) indicators, has the highest significance (AUROC – 0.998). The results indicate involvement of both genetic and cytotoxic mechanisms in the development of uterine fibroids in female workers exposed to toxic industrial aerosols. The models including both two indicators of genotoxicity (micronuclei and protrusion) and one and/or two cytotoxicity indicators have the greatest predictive value.